Adenocarcinoma of the lower esophagus develops almost exclusively in patients with Barrett's esophagus (BE), a condition characterized by the presence of metaplastic columnar epithelium. While the prognosis of patients diagnosed with adenocarcinoma is poor, the chances of successful treatment increase significantly if the disease is detected at the dysplastic stage. The surveillance of patients with BE for dysplasia is challenging in two respects. First, dysplasia is not visible during routine endoscopy. Thus, numerous random biopsies are required. Second, the histopathologic diagnosis of dysplasia is problematic, as there is poor inter-observer agreement on the classification of a particular specimen, even among expert gastrointestinal pathologists. Optical techniques, such as fluorescence, may significantly enhance the endoscopist's ability to detect these early dysplastic changes in BE. Indeed, fluorescence spectroscopy studies using exogenous fluorophores, such as Photofrin® and aminolevulinic-acid induced protoporphyrin IX, show that there is a significant difference between the measured red fluorescence of the carcinomatous and non-dysplastic tissue as a result of the preferential accumulation of the drug. Initial autofluorescence spectroscopy studies performed at 410 nm excitation report promising results for detecting high-grade dysplasia. However, focal high-grade and low-grade lesions could not be detected reliably. Thus a continuing need exists for further improvements in the optical measurements used to detect early stage carcinomas.